| Dicyclanil is a pyrimidine-derived insect growth regulator that inhibits the molting and development of diptera insects and is used in the field of veterinary medicine to prevent myiasis(fly-strike)in sheep.The emulsion as a drug delivery system has many advantages,such as addressing the delivery of water insoluble drugs problems,improving the stability of drugs and has the role of long-lasting.This study developed an emulsion of dicyclanil and established an HPLC method to determine the emulsion,in addition,the stability of the emulsion,physiochemical properties and the safety of dicyclanil emulsion were studied in this paper.Details were as follows:1 Preparation of dicyclanil emulsionThe centrifugal stability constant,the appearance of emulsion and the stability parameter Ke were adopted as the coindicator.Single factor tests and orthogonal designing method were used to investigate the affection of formulation and technological factors to emulsion.The results showed that the optimal formulation was composed by dicyclanil 5%,emulsifier 7%,Aethylis oleas 12.5%,assistant emulsifier 16%and stabilizer 0.35%.Technological conditions in laboratory were optimized,they were emulsifying temperature(50?),high shear speed(20000rpm for 10 min).The emulsion was prepared by a high pressure homogenizing method to practice in pharmaceutical factory under pressure of l0MPa,number of cycle times 3.The prescription was reasonable and the preparation technology was reliable,and can be contributed to the development of the product.2 Development of an HPLC method for the determination of dicyclanil emulsionThe content of the emulsion was determined by using high performance liquid chromatography(HPLC).An C18 column(4.6×250mm,5?m)was used,and the proportion of acetonitrice and water which was added with 0.2%methane acid and 0.6%triethanolamine was 10:90 by the mobile phase.Flow rate was 0.8 mL·min-1,and the column temperature was 30? and the detection wavelength was 267nm,with injection volume of 20?L.Specificity test showed that dicyclanil was undisturbed in the peak position.The linear range of the calibration curve for dicyclanil was 10-100?g·mL-1(R2=0.9999,n=7),taking concentration(C)as the abscissa and peak area(A)for the vertical axis linear regression,and regression equation showed y=148.01x+91.629.The relative standard deviation(RSD)of precision were less than 2%.Prepare nine blank accessories,and then add for the equivalent concentration of the test emulsion of dicyclanil reference 80%,100%and 120%,three copies of each.At the spiked levels of 80%,100%and 120%,the average recovery rate was 98.41%.The dicyclanil was gradually diluted with mobile phase,according to the signal to noise ratio(SNR)3:1 counted as the limit of detection(LOD),and according to SNR 10:1 calculated as the limit of quantification(LOQ).The LOQ and LOD were 20ng·mL1-1 and 10ng·mL-1.Three batches of emulsion were diluted with mobile phase,filtered by the organic membrane,and then inject to detection.The content of dicyclanil was changed to the indicated value content of the sample.The average signal content of the emulsion was 98.57%.The HPLC method has high accuracy and sensitivity and can be used for emulsion of dicyclanil test.3 Physicochemical property and Stability of Dicyclanil EmulsionTo evaluate the quality of dicyclanil emulsion,the stability and physicochemical properties of the emulsion included the particle size,pH value and contents were investigated.The results showed the average particle size,pH and Ke value of the emulsion are 344.3nm,5.17,10.74.Emulsion was centrifuged at speed of 4000 rpm for 15min and no change was found.The related substances of the emulsion are less than 1%.The stability study showed that high temperature and light are less important influential factor on emulsion quality.The content of the emulsion was lower than before after 6months at(3 0± 2)? The physical and chemical stability were good after the long-term testing,the related substances,the content and appearance of the emulsion had no obvious changes.Prescription and preparation of the emulsion selected was consistent with the requirement that instituted by Pharmacopeia and could be produced in factory.4 Experimental study on skin,eyes irritant test of dicyclanil emulsionTo evaluate the safety of dicyclanil emulsion,the irritant test of dicyclanil emulsion on skin and eyes in rabbits were undertaken.Skin and eyes irritation were evaluated by administering dicyclanil emulsion and blank-emulsion to the same body of comparative the left and right of test animals.The results showed that no irritation of dicyclanil emulsion on skin and eyes of rabbit observed.The dicyclanil emulsion was a nonirritating drug and can be used on the animal.5 Acute toxicity study of dicyclanil emulsion in ratsThe acute toxicity by the oral and dermal route in rats by using limit test were investigated in this paper.The results showed an LD50 value after oral administration of more than 500 mg-kg-1.Common signs of toxicity observed were hunched posture,and dyspnoea.All rats had reduced locomotor activity,with ataxia in some Females.The LD50 value after dermal administration was greater than 2 000 mg-kg-1,and no signs of toxicity observed.According to the toxicity grading standards of exogenous chemicals,dicyclanil emulsion was actually low-toxic drug,and can be used on the animal. |
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